Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B

Morris Sherman, Cihan Yurdaydin, Jose Sollano, Marcelo Silva, Yun Fan Liaw, Janusz Cianciara, Anna Boron-Kaczmarska, Paul Martin, Zachary Goodman, Richard Colonno, Anne Cross, Gail Denisky, Bruce Kreter, Robert Hindes

Research output: Contribution to journalArticle

359 Citations (Scopus)

Abstract

Background & Aims: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. Methods: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). Results: Histologic improvement occurred in 55% (68/124) of entecavir-treated vs 28% (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55% (77/141) vs 4% (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log10 copies/mL for entecavir-treated patients and -0.48 log10 copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. Conclusions: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile.

Original languageEnglish
Pages (from-to)2039-2049
Number of pages11
JournalGastroenterology
Volume130
Issue number7
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

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Lamivudine
Hepatitis B e Antigens
Chronic Hepatitis B
Hepatitis B virus
Alanine Transaminase
Therapeutics
entecavir
Viremia
DNA
Viral Load
Antiviral Agents
Safety

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Sherman, M., Yurdaydin, C., Sollano, J., Silva, M., Liaw, Y. F., Cianciara, J., ... Hindes, R. (2006). Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B. Gastroenterology, 130(7), 2039-2049. https://doi.org/10.1053/j.gastro.2006.04.007

Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B. / Sherman, Morris; Yurdaydin, Cihan; Sollano, Jose; Silva, Marcelo; Liaw, Yun Fan; Cianciara, Janusz; Boron-Kaczmarska, Anna; Martin, Paul; Goodman, Zachary; Colonno, Richard; Cross, Anne; Denisky, Gail; Kreter, Bruce; Hindes, Robert.

In: Gastroenterology, Vol. 130, No. 7, 01.07.2006, p. 2039-2049.

Research output: Contribution to journalArticle

Sherman, M, Yurdaydin, C, Sollano, J, Silva, M, Liaw, YF, Cianciara, J, Boron-Kaczmarska, A, Martin, P, Goodman, Z, Colonno, R, Cross, A, Denisky, G, Kreter, B & Hindes, R 2006, 'Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B', Gastroenterology, vol. 130, no. 7, pp. 2039-2049. https://doi.org/10.1053/j.gastro.2006.04.007
Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw YF, Cianciara J et al. Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B. Gastroenterology. 2006 Jul 1;130(7):2039-2049. https://doi.org/10.1053/j.gastro.2006.04.007
Sherman, Morris ; Yurdaydin, Cihan ; Sollano, Jose ; Silva, Marcelo ; Liaw, Yun Fan ; Cianciara, Janusz ; Boron-Kaczmarska, Anna ; Martin, Paul ; Goodman, Zachary ; Colonno, Richard ; Cross, Anne ; Denisky, Gail ; Kreter, Bruce ; Hindes, Robert. / Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B. In: Gastroenterology. 2006 ; Vol. 130, No. 7. pp. 2039-2049.
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abstract = "Background & Aims: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. Methods: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). Results: Histologic improvement occurred in 55{\%} (68/124) of entecavir-treated vs 28{\%} (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55{\%} (77/141) vs 4{\%} (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log10 copies/mL for entecavir-treated patients and -0.48 log10 copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. Conclusions: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile.",
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AU - Sherman, Morris

AU - Yurdaydin, Cihan

AU - Sollano, Jose

AU - Silva, Marcelo

AU - Liaw, Yun Fan

AU - Cianciara, Janusz

AU - Boron-Kaczmarska, Anna

AU - Martin, Paul

AU - Goodman, Zachary

AU - Colonno, Richard

AU - Cross, Anne

AU - Denisky, Gail

AU - Kreter, Bruce

AU - Hindes, Robert

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N2 - Background & Aims: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. Methods: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). Results: Histologic improvement occurred in 55% (68/124) of entecavir-treated vs 28% (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55% (77/141) vs 4% (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log10 copies/mL for entecavir-treated patients and -0.48 log10 copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. Conclusions: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile.

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